The amino acids, carbohydrates, and fats that are utilized by tumors and normal tissues and organs are transported between these tissues by well-defined interorgan transport cycles. In general, these cycles are established so that a metabolic product released from one organ is absorbed and metabolized by another. As an example, glucose and ketone bodies released from the liver and glutamine and lactate released from muscle may be absorbed and oxidized to CO2, alanine, and NH3 by the small intestine. Our recent in vivo experiments have shown that glutamine, glucose, ketone bodies, and lactate are also utilized by fast-growing hepatomas and other tumors. This similarity between respiratory fuels utilized by fast-growing normal and tumor tissues led us to propose that all fast-growing cells have a common pattern of substrate utilization for energy production. In neoplasms a gradual shift from that pattern of substrate utilization typical of the normal tissue to that characteristic of the fast-growing neoplasm develops during tumor progression. Testing this hypothesis and definition of the pathways of energy metabolism in tumors is the long-term goal of this research. The specific aims are to determine the major respiratory fuels of fast-growing tumors, the interactions between these substrates for utilization and oxidation, and the interaction between tumor and host for supply of these fuels to the tumor, especially during cancer cachexia. We will determine the relative importance of glucose, glutamine, the ketone bodies, fatty acids, and lactate as respiratory fuels and as "building blocks" for tumor protoplasm in vivo, during the fed and fasting states. There are now essentially no data on the utilization of these substrates by tumors in vivo. What research has been performed points out the considerable discrepancies between results obtained in vivo and in vitro with regard to tumor energy metabolism and growth of tumors in vivo. (E)